Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
© Hepatitis C Online PDF created October 18, 2016, 10:56 am Treatment of Hepatitis C in Patients with HIV Coinfection Module 6: Lesson 2: Contents: Treatment of Special Populations and Special Situations Treatment of Hepatitis C in Patients with HIV Coinfection Background of HCV-HIV Coinfection Key Studies for Treatment of HCV with HIV Coinfection Recommended HCV Treatment in Patients with HIV Coinfection Drug-Drug Interactions with HIV-HCV Coinfection Treatment Future HCV Treatment Options in Patients with HIV Coinfection Summary Points References Figures Background of HCV-HIV Coinfection Impact of HIV Coinfection in Persons with Chronic Hepatitis C Infection: In the United States, approximately 5 to 10 percent of patients with chronic hepatitis C (HCV) infection are coinfected with HIV. Coinfection with HIV accelerates the progression of hepatic fibrosis and results in a more aggressive course of liver disease (Figure 1). Cirrhosis has been observed to occur 12 to 16 years earlier in those coinfected with HCV and HIV compared with those who have HCV monoinfection. For HIV-infected patients with HCV coinfection, liver-related morbidity and mortality is a prominent non-AIDS-defining complication—up to 90% of liver-related deaths in HIV-infected patients are attributable to HCV. Unfortunately, patients coinfected with HCV and HIV have decreased access to liver transplantation compared with HCV monoinfected patients. For all of these reasons, treatment of HCV in this patient population should have a high priority. Historically, treatment of HCV in patients coinfected with HIV had limited uptake, largely due to a low response rate with interferon-based therapy, a high rate of adverse effects, concerns for interactions with antiretroviral medications, and high prevalence of comorbidities, such as psychiatric conditions and chemical dependency. The recent availability of highly effective all-oral HCV regimens has generated major enthusiasm and interest for the treatment of HCV in persons coinfected with HIV. Historic Approach to Treatment: For patients coinfected with HCV and HIV, initial trials with interferon monotherapy or dual therapy with standard interferon plus ribavirin were associated with very low SVR rates and significant toxicity. Response rates were higher with peginterferon and ribavirin in coinfected patients, but still suboptimal, as summarized in a table format (Figure 2) and a graph illustration (Figure 3). The peginterferon and ribavirin combination regimen had particularly low SVR rates among those with genotype 1 HCV (typically less than 30%). Further, the SVR rates with peginterferon and ribavirin was 15 to 25% lower in coinfected patients than in HCV monoinfected patients. In 2011, the addition of a first-generation HCV protease inhibitor (telaprevir or boceprevir) to peginterferon and ribavirin improved SVR rates with GT1 to approximately 60% and narrowed the gap in treatment response between coinfected and monoinfected patients to approximately 15%. This triple therapy regimen, however, proved to be quite complex and challenging due to interactions with antiretroviral medications, greater pill burden, food requirements, and additional adverse effects. With the advent of all-oral regimens that include new direct acting antiviral agents (DAAs) that are safe, highly effective, and have fewer drug interactions, the older regimens of peginterferon and ribavirin or peginterferon and ribavirin plus a firstgeneration protease inhibitor are no longer recommended for treatment of HCV in coinfected patients. 1 / 19 Key Studies for Treatment of HCV with HIV Coinfection Changing Landscape of Treatment in Coinfected Patients: The introduction of direct-acting antiviral agents (DAAs), and in particular, interferon-free combination therapy, has changed the landscape of therapy for patients coinfected with HCV and HIV. Several studies using DAA-based therapy have demonstrated comparable rates of sustained virologic response in coinfected and monoinfected patients (Figure 4), providing convincing evidence that coinfected patients may no longer require the designation of a special or “treatment refractory” population. It should be noted that these trial participants included primarily individuals without cirrhosis and those with high CD4 cell counts, usually well above the threshold of 200 cells/mm3. Ultimately, clinical efficacy in more heterogeneous cohorts of coinfected patients will need to be demonstrated. The following provides a summary of key studies (in alphabetical order) that have involved treatment of hepatitis C infection in patients who have HIV coinfection. Click on the study name to see more details and summary PowerPoint slides. ALLY-2: In the phase 3, randomized, multi-center ALLY-2 trial, investigators enrolled 203 HIVHCV coinfected patients to receive HCV treatment with daclatasvir plus sofosbuvir. Treatment-naive patients were randomized to receive either an 8-week or 12-week treatment course, whereas all treatment-experienced patients received a 12-week course. Patients with HCV genotype 1, 2, 3, or 4 were eligible. The HIV entry criteria required a CD4 count greater than 350 cells/mm3 if the patient was not taking antiretroviral therapy or at least 100 cells/mm3 if on antiretroviral therapy and an HIV RNA less than 50 copies/ml. The SVR 12 rates were excellent with the 12-week regimens (96% in treatment-naive and 98% in treatment-experienced patients) but only 76% in the 8-week regimen for treatment-naive patients. C212: This open-label phase 3 trial evaluated the effectiveness of simeprevir with peginterferon and ribavirin (weight-based dosing) in both treatment-naïve (n=53) and treatment-experienced (n=63) HIV/HCV coinfected patients with chronic HCV genotype 1. The overall SVR12 rate was 74% to 79% among treatment-naïve patients and 57% among prior null responders. C-EDGE Coinfection: In this prospective single-arm, open-label clinical trial, investigators enrolled 218 patients with chronic hepatitis C genotype 1, 4, or 6 and HIV coinfection for treatment with a 12-week course of elbasvir-grazoprevir once daily for 12 weeks. Among those enrolled, 86% had genotype 1a or 1b infection and 35 (16%) had compensated cirrhosis. The overall SVR12 rate was 96% by primary analysis, with the breakdown by genotype showing 96.5% for genotype 1a, 95.5% for genotype 1b, and 96.4% for genotype 4. All cirrhotic patients achieved an SVR12. NIAID ERADICATE: This phase 2 trial investigated the open-label use of ledipasvir-sofosbuvir for 12 weeks in 50 treatment-naïve patients with genotype 1 chronic HCV and HIV coinfection. Among the 50 patients enrolled, 13 were not on antiretroviral therapy and 37 were receiving antiretroviral therapy (medications allowed included tenofovir-emtricitabine, efavirenz, and rilpivirine). Overall, 49 (98%) of patients in the study achieved an SVR12. ION-4: In this phase 3, open-label, multicenter study, investigators enrolled 335 patients with hepatitis C genotype 1 or 4 who were coinfected with HIV to receive a 12-week course of ledipasvir-sofosbuvir. Enrollment included HCV treatment-naive and experienced patients and those without cirrhosis and those with compensated cirrhosis. The HIV enrollment criteria consisted of HIV RNA less than 50 copies/ml, CD4 count greater than 100 cells/mm3; antiretroviral regimens could include tenofovir-emtricitabine plus either efavirenz, rilpivirine, or raltegravir. Overall, 321 (96%) of 335 treated patients achieved an SVR12. The results were similar regardless of prior treatment status or presence of cirrhosis. PHOTON-1: This open label, nonrandomized, uncontrolled, phase 3 trial evaluated 223 patients with chronic hepatitis C genotypes 1, 2, or 3 and HIV coinfection. This trial examined the efficacy of the all-oral regimen of sofosbuvir plus ribavirin (weight-based) in treatmentnaive and treatment-experienced patients. Patients in the trial were required to be on stable antiretroviral therapy with an undetectable HIV RNA level and CD4 count greater than 200 2 / 19 cells/mm3, or if untreated, they had CD4 count greater than 500 cells/mm3. The trial included treatment-naive patients with genotype 1, 2, or 3 and treatment-experienced patients with genotype 2 or 3. A 24-week treatment course was given to all patients with HCV genotype 1 and to treatment-experienced patients with HCV genotype 2 or 3; treatment-naive patients with HCV genotype 2 or 3 received a 12-week treatment course. Patients with cirrhosis were included in the trial, but could not comprise more than 20% of the total number of subjects enrolled. For treatment-naive patients, the SVR12 rates were 76% with genotype 1, 88% with genotype 2, and 67% with genotype 3. Treatment-experienced patients with genotype 2 had a 92% SVR12 rate and those with genotype 3 had a 94% SVR12 rate. PHOTON-2: In this open-label, phase 3 trial, 274 HIV-infected patients coinfected with HCV genotype 1,2,3, or 4 received treatment with the all-oral regimen of sofosbuvir plus weightbased ribavirin. The study enrolled treatment-naive patients with genotypes 1, 2, 3, or 4 and treatment-experienced with genotype 2 or 3. A 24-week treatment course was given to all patients with HCV genotype 1, 3, or 4 and treatment-experienced patients with genotype 2, whereas treatment-naïve with HCV genotype 2 received 12 weeks. Among those enrolled, 81% of the patients were HCV treatment naïve and 20% had cirrhosis. The mean CD4 count was 588 cells/mm3 and 97% were on antiretroviral therapy (tenofovir-emtricitabine plus one of the following: efavirenz, atazanavir plus ritonavir, darunavir plus ritonavir, rilpivirine, or raltegravir). The SVR 12 rates were high with all HCV genotypes: GT1 (85%), GT2 (88%), GT3 (89%), and GT4 (84%). In addition, the treatment responses were similar in the treatmentnaïve and treatment-experienced patients. Sofosbuvir for Genotype 1-4 in HIV Coinfection: In this single-arm, single-site, open-label trial, 23 HCV/HIV coinfected treatment-naïve patients with genotype 1-4 received the 12-week triple therapy of peginterferon alfa-2a, ribavirin (weight-based), and sofosbuvir. Mean CD4 count was 562 cells/mm3 and all were on antiretroviral therapy (tenofovir-emtricitabine plus one of the following: efavirenz, atazanavir plus ritonavir, darunavir plus ritonavir, rilpivirine, or raltegravir). The overall SVR12 rate was 91%; of the 19 patients with genotype 1, 89% achieved an SVR12. TURQUOISE-I This open-label study randomized treatment-naïve and experienced patients with chronic HCV genotype 1 patients with HIV coinfection to receive a 12- or 24-week course of ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin. Patients were required to have a CD4 count of at least 200 cells/mm3 (or CD4% greater than 13) and an HIV RNA level less than 40 copies while receiving an atazanavir- or raltegravir-based regimen. Enrollment included patients with compensated cirrhosis (Child-Pugh class A) and patients with prior treatment with peginterferon plus ribavirin. The SVR12 rates were 29 (93.5%) of 31 in the 12-week group and 29 (90.6%) of 32 in the 24-week group. Recommended HCV Treatment in Patients with HIV Coinfection Timing of Antiretroviral Therapy in Context of HCV Therapy: The 2015 HIV Department of Health and Human Services (DHHS) Guidelines on the use of antiretroviral therapy emphasizes the following key points regarding antiretroviral therapy for persons coinfected with HIV and HCV: Antiretroviral therapy should be considered for most patients with HIV and HCV coinfection, regardless of their CD4 cell count. This recommendation is supported by observational studies that suggest antiretroviral therapy may slow liver disease progression and reduce the risk of liver-related morbidity. In antiretroviral-naive patients with a CD4 count greater than 500 cells/mm3, antiretroviral therapy could be deferred until after treatment of HCV. For those patients whose CD4 counts are less than 200 cells/mm3 it may be advisable to first initiate antiretroviral therapy and defer HCV therapy until the patient is stable on antiretroviral therapy. Factors to Consider Prior to Choosing HCV Treatment Regimen: In persons coinfected with 3 / 19 HIV, the major factors in selecting a regimen to treat HCV include HCV genotype, prior treatment experience, presence of cirrhosis, and potential drug interactions with the HIV antiretroviral medications. Of note, the preponderance of clinical trial data on the efficacy of HCV therapy derive from patients on antiretroviral therapy with suppressed HIV RNA levels and CD4 counts greater than 200 cells/mm3. AASLD/IDSA Guidance: The guidance from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America addresses the treatment of patients with HIV/HCV coinfection in detail (see Unique Patient Populations: Patients with HIV/HCV Coinfection). For a summary of the recommendations for the treatment of HCV in persons coinfected with HIV, including recommendations related to HCV medication interactions with antiretroviral medications, see the Summary Box. The AASLD/IDSA guidance recommends using the same approach for HCV treatment in persons coinfected with HIV as those with HCV monoinfection, but noting that important drug-drug interactions between HCV medications and HIV antiretroviral medications need to be recognized and managed. In the HCV guidance, older regimens, such as peginterferon plus ribavirin or peginterferon plus ribavirin plus either boceprevir, telaprevir, or simeprevir are not recommended for use in any circumstance, due to suboptimal SVR rates, long duration of therapy, and poor tolerance. Drug-Drug Interactions with HIV-HCV Coinfection Treatment Most persons coinfected with HCV and HIV are taking multi-drug antiretroviral therapy, which may pose a problem with drug-drug interactions when initiating therapy with HCV medications. See the summary table (Figure 5) from the drug interactions section in the HHS Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Note that daclatasvir was not FDA approved for use in the United States at the time these tables were last updated. The following provides key points related to drug-drug interaction for each HCV medication listed below. Daclatasvir: The NS5A inhibitor daclatasvir is a substrate of CYP3A. When daclatasvir is given with a CYP3A inhibitor, the levels of daclatasvir can increase, particularly with strong inhibitors of CYP3A. The dose of daclatasvir should therefore be reduced to 30 mg when used with either ritonavir-boosted atazanavir or lopinavir. In contrast, when used with efavirenz, a CYP3A inducer, the dose of daclatasvir should be increased to 90 mg daily. Ledipasvir-Sofosbuvir: The NS5A inhibitor ledipasvir is not metabolized by the cytochrome p450 system, but is a substrate of p-glycoprotein. Ledipasvir increases tenofovir levels by 1.3 to 2.6 fold when concomitantly given with either rilpivirine or efavirenz. Although ledipasvir administered concomitantly with tenofovir and an HIV protease inhibitor has not been studied, there is concern that tenofovir levels may increase substantially with this combination. Because of this concern and lack of data, the use of ledipasvir with ritonavirboosted HIV protease inhibitors should, if possible, be avoided. For similar reasons, ledipasvirsofosbuvir should not be used with cobicistat, elvitegravir, or tipranavir. Ledipasvir-sofosbuvir should not be used in HIV-infected patients on tenofovir if the baseline creatinine clearance is less than 60 ml/min. Ombitasvir-Paritaprevir-Ritonavir: The major concern for drug interaction with this regimen is the significant p450 inhibition generated by ritonavir. This combination regimen should not be used with efavirenz, rilpivirine, darunavir, or lopinavir-ritonavir. Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir: The major concern for drug interaction with this regimen is the significant p450 inhibition generated by ritonavir. This combination regimen should not be used with efavirenz, rilpivirine, darunavir, or lopinavirritonavir. Peginterferon alfa: The metabolism of peginterferon alfa occurs predominantly via CYP1A2. No major drug-drug interactions exist with peginterferon and antiretroviral medications. Ribavirin: Significant and serious toxic drug-drug interactions and severe toxicities can occur with the simultaneous use of ribavirin and certain HIV nucleoside reverse transcriptase 4 / 19 inhibitors. The use of ribavirin with didanosine is strictly contraindicated due to a marked increase in intracellular didanosine levels, which may cause hepatic failure, pancreatitis, and lactic acidosis. This can also occur with stavudine or zidovudine. Thus, simultaneous use of ribavirin with either didanosine, stavudine, or zidovudine should be avoided. Concurrent use of ribavirin and zidovudine should also be avoided because of additive hematologic toxicity and increased risk of severe anemia with this combination. Simeprevir: This NS34A HCV protease inhibitor has complex interactions with antiretroviral medications because it is a substrate and an inhibitor of CYP3A4 and p-glycoprotein. In addition, simeprevir inhibits the OATP1B1/3 drug transporter. Simeprevir should not be used concomitantly with any of the following medications: efavirenz, etravirine, nevirapine, any HIV protease inhibitors, or any regimen that contains cobicistat. Simeprevir can be used with reverse transcriptase inhibitors, rilpivirine, dolutegravir, and raltegravir; if used with maraviroc, the dose of maraviroc should be decreased to 150 mg twice daily. Sofosbuvir: This NS5B polymerase inhibitor is rapidly converted to a dominant circulating metabolite (GS-331007). Sofosbuvir is not metabolized by the cytochrome p450 system, but is a substrate of p-glycoprotein. The only significant interaction with antiretroviral medications occurs with the p-glycoprotein inducer tipranavir, which may decrease levels of sofosbuvir and the GS-331007 metabolite. Accordingly sofosbuvir should not be used concomitantly with tipranavir, but it can be use with all other antiretrovirals. Future HCV Treatment Options in Patients with HIV Coinfection Several all-oral investigational regimens have shown promising preliminary results for the treatment of HCV in persons coinfected with HIV. Grazoprevir-Elbasvir: Grazoprevir is an NS3/4A protease inhibitor under study with elbasvir, an NS5A replication complex inhibitor. In the phase 3, open label C-EDGE trial, investigators treated 218 treatment-naive patients with genotype 1, 4, or 6 HCV (and HIV coinfection) with a 12-week course of the once daily fixed-dose combination of grazoprevir (100 mg) and elbasvir (50 mg). Patients were eligible to enroll if (a) they were on antiretroviral therapy for at least 8 weeks, had an undetectable HIV RNA level, and had a CD4 count greater than 200 cells/mm3 or (b) they had a CD4 count greater than 500 cells/mm3 and an HIV RNA level less than 50,000 copies/ml. Overall, 210 (96%) of 218 patients achieved an SVR12. Analysis for all patients showed similar SVR rates with genotype 1a, 1b, and 4. The regimen was well tolerated, including patients with cirrhosis. Summary Points In patients with chronic hepatitis C, coinfection with HIV can accelerate the progression of hepatic fibrosis. Therefore, treatment of HCV should have high priority in coinfected patients. The introduction of direct-acting antiviral agents (DAAs), and in particular interferon-free combination therapy, has changed the landscape of therapy for patients coinfected with HCV and HIV, with multiple studies demonstrating comparable rates of sustained virologic response in coinfected and monoinfected patients. The AASLD/IDSA HCV Guidance recommends using the same HCV treatment approach for patients coinfected with HIV as those with HCV monoinfection, except that in coinfected patients special consideration should be given to monitoring and managing drug-drug interactions. The use of peginterferon and ribavirin alone or peginterferon and ribavirin plus either boceprevir or telaprevir is no longer recommended for treatment of HCV in coinfected patients (or HCV monoinfected patients) in HIV-infected patients (or HCV monoinfected patients). 5 / 19 Antiretroviral therapy may slow liver disease progression in HIV/HCV coinfected patients and should therefore be considered for all coinfected patients regardless of CD4 cell count. For coinfected patients whose CD4 cell counts are less than 200 cells/mm3, it may be advisable to wait for further immune reconstitution prior to initiating HCV therapy, particularly since most HCV treatment trials have excluded such patients. 6 / 19 References AASLD/IDSA. Recommendations for testing, management, and treating hepatitis C. Unique patient populations: patients with HIV/HCV confection. [AASLD/IDSA Hepatitis C Guidance] Avidan NU, Goldstein D, Rozenberg L, et al. Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts. J Acquir Immune Defic Syndr. 2009;52:452-8. [PubMed Abstract] Berenguer J, González-García J, López-Aldeguer J, et al. Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients. J Antimicrob Chemother. 2009;63:1256-63. [PubMed Abstract] Bichoupan K, Dieterich DT, Martel-Laferrière V. HIV-hepatitis C virus co-infection in the era of direct-acting antivirals. Curr HIV/AIDS Rep. 2014;11:241-9. [PubMed Abstract] Cachay ER, Hill L, Wyles D, et al. The hepatitis C cascade of care among HIV infected patients: a call to address ongoing barriers to care. PLoS One. 2014;9:e102883. [PubMed Abstract] Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839-48. [PubMed Abstract] Centers for Disease Control and Prevention (CDC). Sexual transmission of hepatitis C virus among HIV-infected men who have sex with men--New York City, 2005-2010. MMWR Morb Mortal Wkly Rep. 2011;60:945-50. [CDC and MMWR] Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451-9. [PubMed Abstract] Di Martino V, Rufat P, Boyer N, et al. The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study. Hepatology. 2001;34:1193-9. [PubMed Abstract] Dieterich D, Nelson M, Soriano V, et al. Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV. AIDS. 2015;29:571-81. [PubMed Abstract] Dieterich D, Rockstroh JK, Orkin C, et al. Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study. Clin Infect Dis. 2014;59:1579-87. [PubMed Abstract] European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. 7 / 19 [EASL] Hagan LM, Sulkowski MS, Schinazi RF. Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon-ineligible/intolerant individuals. Hepatology. 2014;60:37-45. [PubMed Abstract] Joshi D, O'Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet. 2011;377:1198-209. [PubMed Abstract] Kirk GD, Mehta SH, Astemborski J, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013;158:658-66. [PubMed Abstract] Kohli A, Osinusi A, Sims Z, et al. Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study. Lancet. 2015;385:1107-13. [PubMed Abstract] Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370:1879-88. [PubMed Abstract] Laguno M, Cifuentes C, Murillas J, et al. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology. 2009;49:22-31. [PubMed Abstract] Laguno M, Murillas J, Blanco JL, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18:F27-36. [PubMed Abstract] Martel-Laferrière V, Brinkley S, Bichoupan K, et al. Virological response rates for telaprevirbased hepatitis C triple therapy in patients with and without HIV coinfection. HIV Med. 2013;15:108-15. [PubMed Abstract] Molina JM, Orkin C, Iser DM, et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015;385:1098-106. [PubMed Abstract] Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:705-13. [PubMed Abstract] Núñez M, Miralles C, Berdún MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007;23:972-82. [PubMed Abstract] Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013;310:804-11. 8 / 19 [PubMed Abstract] Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313:1232-9. [PubMed Abstract] Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Considerations for antiretroviral use in patients with confections: hepatitis C (HCV)/HIV confection. April 8, 2015. [AIDSinfo] Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis C virus infection. October 28, 2014. [AIDSinfo] Piroth L, Paniez H, Taburet AM, et al. High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study. Clin Infect Dis. 2015;61:817-25. [PubMed Abstract] Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE COINFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2:e319-27. [PubMed Abstract] Rockstroh JK, Spengler U. HIV and hepatitis C virus co-infection. Lancet Infect Dis. 2004;4:437-44. [PubMed Abstract] Rodriguez-Torres M, Gaggar A, Shen G, et al. Sofosbuvir for chronic hepatitis C virus infection genotype 1-4 in patients coinfected with HIV. J Acquir Immune Defic Syndr. 2015;68:543-9. [PubMed Abstract] Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus coinfection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385:1087-97. [PubMed Abstract] Sulkowski M, Pol S, Mallolas J, et al. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis. 2013;13:597-605. [PubMed Abstract] Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313:1223-31. [PubMed Abstract] - 9 / 19 Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014;312:353-61. [PubMed Abstract] Sulkowski MS, Poordad F, Manns MP, et al. Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial. Hepatology. 2013;57:974-84. [PubMed Abstract] Sulkowski MS, Sherman KE, Dieterich DT, et al. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med. 2013;159:86-96. [PubMed Abstract] Thomas DL, Bartlett JG, Peters MG, Sherman KE, Sulkowski MS, Pham PA. Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIVinfected persons. Clin Infect Dis. 2012;54:979-83. [PubMed Abstract] Thomas DL. The challenge of hepatitis C in the HIV-infected person. Annu Rev Med. 2008;59:473-85. [PubMed Abstract] Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438-50. [PubMed Abstract] Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:714-25. [PubMed Abstract] - 10 / 19 Figures Figure 1 Progression to Cirrhosis in Patients with HCV Monoinfection and HCV-HIV Coinfection This graph shows accelerated progression to cirrhosis in patients with HIV-HCV coinfection when compared with those with HCV monoinfection. Source: Di Martino V, Rufat P, Boyer N, et al. The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study. Hepatology. 2001;34:1193-9. 11 / 19 Figure 2 Summary Table of HCV-HIV Coinfection Studies using Peginterferon plus Ribavirin 1. Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451-9. 2.Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438-50. 3. Laguno M, Murillas J, Blanco JL, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18:F27-36. 4. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839-48. 5.Núñez M, Miralles C, Berdún MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007;23:972-82. 5.Núñez M, Miralles C, Berdún MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007;23:972-82. 12 / 19 Figure 3 Key HCV-HIV Coinfection Studies using Peginterferon plus Ribavirin Source 1. Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451-9. 2.Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438-50. 3. Laguno M, Murillas J, Blanco JL, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18:F27-36. 4. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839-48. 5.Núñez M, Miralles C, Berdún MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007;23:972-82. 13 / 19 Figure 4 SVR Rates in Treatment-Naive Patients with HCV-HIV Coinfection versus HCV Monoinfection 1. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:714-25. 2. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211-21. 3. Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:705-13. 4. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889-98. 5. Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313:1223-31. 6. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370:1983-92.1. Dieterich D, Rockstroh JK, Orkin C, et al. 7. Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2:e319-27. 8. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for TreatmentNaive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015;163:1-13. 14 / 19 Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications (Image Series) - Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications Image 5A: HCV DAAs and HIV Nucleoside Reverse Transcriptase Inhibitors Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Drug interactions: drug interactions between nucleoside reverse transcriptase inhibitors and other drugs. April 8, 2015. 15 / 19 Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications Image 5B: HCV DAAs and HIV Non-nucleoside Reverse Transcriptase Inhibitors Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Drug interactions: drug interactions between non-nucleoside reverse transcriptase inhibitors and other drugs. April 8, 2015. 16 / 19 Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications Image 5C: HCV DAAs and HIV Protease Inhibitors Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Drug interactions: drug interactions between protease inhibitors and other drugs. April 8, 2015. 17 / 19 Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications Image 5D: HCV DAAs and HIV Integrase Strand Transfer Inhibitors Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Drug interactions: drug interactions between integrase inhibitors and other drugs. April 8, 2015. 18 / 19 Figure 5 (Image Series) - Interactions with HIV Antiretroviral and HCV Medications Image 5E: HCV DAAs and HIV CCR5 Antagonist Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Drug interactions: drug interactions between CCR5 antagonist and other drugs. April 8, 2015. 19 / 19 Powered by TCPDF (www.tcpdf.org)